This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABSTRACT Extremely low birth weight (ELBW) newborns (birth weight <1000g), usually require Total Parenteral Nutrition (TPN) during the course of their illness and until their ability to tolerate enteral feeds is well established. These infants are at risk of disturbed glucose metabolism and inadequate energy supplementation. They have a very high incidence of hyperglycemia (50-80%). Usually, these high blood glucose values are being treated with reduction of the glucose infusion rate and/or with intravenous insulin, depending on the severity of the hyperglycemia and the patient's clinical picture. We do not know whether gluconeogenesis is affected by the changes in glucose and insulin concentrations resulting from reduced glucose infusion rates or by a fixed insulin infusion. the purpose of this study is to determine the effect of reducing the glucose infusion rate to correspond to half the normal glucose turn over rate and of a fixed insulin infusion, on glucose and protein metabolism in ELBW infnats. It is important for us to learn about the physiology of glucose metabolism in these very small infants for it will enable us to design an adequate parenteral nutrition that renders these infants normoglycemic while providing a sufficient energy intake. HYPOTHESIS 1. Rates of gluconeogenesis do not change in response to a decrease in blood levels of glucose and insulin, resulting from a decrease in the glucose infusion rate to 3mg/kg/min. 2. A fixed infusion of insulin sufficient to achieve a plasma insulin concentration in the high physiologic range (-80-100uU/ml) will: a. Not acutely suppress rates of gluconeogenesis b. Increase glucose utilization regardless of body weight, gestational age and clinical status, but increasing the glucose utilization will be proportional to body weight c. Increase protein synthesis SPECIFIC AIMS The purpose of this study is to determine the metabolic effects of changes in glucose and insulin concentration resulting from reducing the infusion rate of glucose to correspond to half normal glucose turnover (while maintaining the infusion rates of parenteral lipids and amino acids unchanged) and from a fixed insulin infusion on rates of glucose utilization and production in extremely low birth weight infants. This will be performed using Stable Isotope-GCMS techniques. This will allow us to determine the metabolic effects of different glucose infusion rates and plasma insulin levels in sick newborn infants.